Recombinant Oxytocin
Oxytocin, often referred to as the bonding chemical, is a hormone secreted by the posterior region of the pituitary gland known as the neurohypophisis. Hormones secreted from this region are aptly classified as neurohypophysial and include oxytocin, vasopressin, mesotocin, and others (1). Oxytocin function was first elucidated by Sir Henry Hallet Dale in 1906, when he noted the hormone's ability to induce uterine contractions. In 1953 Vincent du Vigneaud determined the nine amino acid sequence of oxytocin and was able to synthesize the nuero peptide (2). Vigneaud received the nobel prize in chemistry for his work, as oxytocin was the first hormone to be sequenced and synthesized. Synthesized Oxytocin - Clinical Application Oxytocin synthesis is relatively easy due to the short length of the peptide chain. Synthesized oxytocin comes in brand name forms such as Pitocin and Syntocinon. The synthetic form of the molecule is has been, and is increasingly being, used for labor induction and augmentation (3). Labor induction is most recognized in the treatment of post term pregnancy, but can also be necessary in many other scenarios such as maternal medical conditions, fetal compromise, premature rupture of membranes, and many more (3). While some health professionals criticize the overuse of oxytocin as cavalier and bypassing a natural process, it has been shown repeatedly to be a important medical tool in specific situations. Recombinant Oxytocin - Research Avenues The relative ease with which oxytocin can be synthesized allowed for it to be applied clinically long before a recombinant form of the drug was created. However, oxytocin has been implicated in a number of other physiological processes/events such as sexual reproduction, orgasm, social recognition, pair bonding, anxiety, and maternal behaviors (1). In order to tease apart the more subtle functions of the oxytocin molecule a recombinant form of the protein was made. Oxytocin Recombination In order to recombine oxytocin a cassette with an internal ribosomal entry sequence paired with a Cre recombinase and a Frt-flanked kanamyacin resistance gene were targeted downstream of the stop codon for oxytocin gene in a bacterial artificial chromosome (4). Long range PCR and southern blot analysis was used to identify successfully recombined clones, which were then injected into blastocysts. The chimeric progeny were then bred for the altered germline oxytocin allele (4). While this recombinant form of oxytocin is not used in the same way many traditional recombinant proteins are, it still has great value. Many studies have used the recombinant forms to look at varying aspects of oxytocin function, as the Cre recombinase domains added into the protein allow for conditional knockout. References 1. http://en.wikipedia.org/wiki/Oxytocin http://en.wikipedia.org/wiki/Oxytocin 2.THE SYNTHESIS OF AN OCTAPEPTIDE AMIDE WITH THE HORMONAL ACTIVITY OF OXYTOCIN. Vincent du Vigneaud, Charlotte Ressler, College John M. Swan, Carleton W. Roberts, Panayotis G. Katsoyannis, and Samuel Gordon. Journal of the American Chemical Society 1953 75 (19), 4879-4880 3. Simpson KR. 2011. Clinicians’ Guide to the Use of Oxytocin for Labor Induction and Augmentation. The Journal of Midwifery & Women’s Health 56: 214-21 4. Wu Z, Xu Y, Zhu Y, Sutton AK, Zhao R, et al. (2012) An Obligate Role of Oxytocin Neurons in Diet Induced Energy Expenditure. PLoS ONE 7(9): e45167. doi:10.1371/journal.pone.0045167